Objective:To investigate the impact and potential mechanisms of Sorbin and SH3 domain-containing protein 2 (Sorbs2) on ventricular arrhythmias in mice.Methods:In the animal experiments, mating was performed using six 8-week-old Sorbs2 +/- mice (3 males and 3 females) weighing 20-22 g. Wild-type (Sorbs2 +/+, n=8) and homozygous (Sorbs2 -/-, n=6) offspring were selected as experimental subjects through genotyping. Echocardiography was performed at 16 weeks of age to record cardiac function parameters in both groups. Resting-state and caffeine-dobutamine-induced electrocardiograms were also conducted. Real-time quantitative reverse transcription polymerase chain reaction was used to detect Sorbs2 messenger RNA expression in the heart, liver, spleen, lung, kidney, brain, small intestine, and skeletal muscle tissues of wild-type mice. Western blotting was employed to measure the protein expression levels of Sorbs2 and voltage-dependent sodium channel alpha subunit 1.5 (Na v1.5) in myocardial tissues from both groups. In the cell experiments, H9C2 cells were transfected with Sorbs2 small interfering RNA as the si-Sorbs2 group, with a corresponding si-negative control group established. Western blot was performed to detect the protein expression levels of Sorbs2 and Na v1.5 in both groups. Results:Sorbs2 was abundantly expressed in cardiac tissue. Compared with wild-type mice, homozygous mice exhibited larger left ventricular end-systolic diameter, along with lower left ventricular ejection fraction and fractional shortening ( P all<0.05). Resting-state electrocardiograms revealed no spontaneous arrhythmias in either group; however, homozygous mice showed shorter RR intervals but longer QRS and QTc intervals versus wild-type mice ( P all<0.05). Following caffeine and dobutamine induction, homozygous mice demonstrated a higher incidence of ventricular arrhythmias, longer arrhythmia duration, and higher ventricular arrhythmia scores than wild-type mice ( P all<0.05). Western blot analysis revealed that Na v1.5 protein expression was markedly lower in myocardial tissues of homozygous mice compared to wild-type mice. Similarly, si-Sorbs2-transfected H9C2 cells exhibited lower Na v1.5 protein levels compared to the si-negative control group ( P<0.05). Conclusion:Sorbs2 plays a critical role in maintaining normal cardiac electrophysiological function. Deficiency of Sorbs2 may lead to impaired cardiac function and increased susceptibility to ventricular arrhythmias in mice, which could be associated with reduced expression of Na v1.5 protein.

Cardiac arrest is a major health event that poses a major threat to human life and health.Post-cardiac arrest brain injury is the main adverse prognostic factor and cause of death in patients who experience cardiac arrest.Currently,the therapeutic methods and effects are limited.In recent years,with the in-depth research on microbiota-gut-brain communication,it has been found that intestinal microbiota and their metabolites may play a role in the regulation of neuroinflammation in post-cardiac arrest brain injury.Short-chain fatty acids are the key substances in microbiota-gut-brain communication,and the mechanism involves immune,endocrine and neuroregulatory pathways.Supplementation of short-chain fatty acid-producing bacteria or short-chain fatty acids can improve intestinal flora disorder and reduce neuroinflammation after cardiopulmonary resuscitation.As a key mediator in microbial-gut-brain communication,short-chain fatty acids have great potential for the treatment of brain injury after cardiac arrest.This review explores the role and regulatory mechanism of microbiota-gut-brain communication in the neuroinflammation of brain injury after cardiopulmonary resuscitation through immune,endocrine and neuro-regulatory pathways,providing a new idea for the treatment of post-cardiac arrest brain injury.

Objective To investigate the influencing factors of secondary coagulation dysfunction in patients with severe acute pancreatitis(SAP)and establish the prediction model.Methods A total of 298 SAP patients in our hospital from July 2021 to July 2024 were consecutively selected,and those with secondary coagulation dysfunction were included in the observation group,while those without secondary coagulation dysfunction were included in the control group.Multivariate Logistic regression analysis was employed to investigate the risk factors for secondary coagulation dysfunction in patients with SAP and to establish a multivariate joint prediction model.The receiver operating characteristic curve(ROC)and decision curve were used to evaluate the predictive value of the multivariate joint prediction model for secondary coagulation dysfunction in SAP patients.Results The incidence of secondary coagulation dysfunction in SAP patients was 32.21%.The activated partial thromboplastin time(APTT),prothrombin time(PT)and fibrinogen(FIB)were longer in the observation group than those in the control group(P<0.05).Acute physiological and chronic health score Ⅱ(APACHEⅡ)score,sequential organ failure assessment(SOFA)score,D-dimer,C-reactive protein and albumin were independent influencing factors of secondary coagulation dysfunction in SAP patients(P<0.05).The regression equation model was established according to the results of multivariate analysis screened variables,logit(P)=-24.747+0.363×APACHEⅡ score+0.952×SOFA score-0.449×albumin+1.768×D-dimer+1.004×C-reactive protein,with a good fit.Regression model predicted that the AUC value of secondary coagulation dysfunction in SAP patients was 0.937.Decision curve analysis results showed that the Logistic regression model could achieve the maximum clinical benefit when the threshold probability was in the range of 0.06 to 0.97.Conclusion A comprehensive assessment of influencing factors can comprehensively evaluate the condition of patients and identify patients at high risk of coagulation disorders at an early stage.

Cardiac arrest is a major health event that poses a major threat to human life and health.Post-cardiac arrest brain injury is the main adverse prognostic factor and cause of death in patients who experience cardiac arrest.Currently,the therapeutic methods and effects are limited.In recent years,with the in-depth research on microbiota-gut-brain communication,it has been found that intestinal microbiota and their metabolites may play a role in the regulation of neuroinflammation in post-cardiac arrest brain injury.Short-chain fatty acids are the key substances in microbiota-gut-brain communication,and the mechanism involves immune,endocrine and neuroregulatory pathways.Supplementation of short-chain fatty acid-producing bacteria or short-chain fatty acids can improve intestinal flora disorder and reduce neuroinflammation after cardiopulmonary resuscitation.As a key mediator in microbial-gut-brain communication,short-chain fatty acids have great potential for the treatment of brain injury after cardiac arrest.This review explores the role and regulatory mechanism of microbiota-gut-brain communication in the neuroinflammation of brain injury after cardiopulmonary resuscitation through immune,endocrine and neuro-regulatory pathways,providing a new idea for the treatment of post-cardiac arrest brain injury.

Objective To investigate the influencing factors of secondary coagulation dysfunction in patients with severe acute pancreatitis(SAP)and establish the prediction model.Methods A total of 298 SAP patients in our hospital from July 2021 to July 2024 were consecutively selected,and those with secondary coagulation dysfunction were included in the observation group,while those without secondary coagulation dysfunction were included in the control group.Multivariate Logistic regression analysis was employed to investigate the risk factors for secondary coagulation dysfunction in patients with SAP and to establish a multivariate joint prediction model.The receiver operating characteristic curve(ROC)and decision curve were used to evaluate the predictive value of the multivariate joint prediction model for secondary coagulation dysfunction in SAP patients.Results The incidence of secondary coagulation dysfunction in SAP patients was 32.21%.The activated partial thromboplastin time(APTT),prothrombin time(PT)and fibrinogen(FIB)were longer in the observation group than those in the control group(P<0.05).Acute physiological and chronic health score Ⅱ(APACHEⅡ)score,sequential organ failure assessment(SOFA)score,D-dimer,C-reactive protein and albumin were independent influencing factors of secondary coagulation dysfunction in SAP patients(P<0.05).The regression equation model was established according to the results of multivariate analysis screened variables,logit(P)=-24.747+0.363×APACHEⅡ score+0.952×SOFA score-0.449×albumin+1.768×D-dimer+1.004×C-reactive protein,with a good fit.Regression model predicted that the AUC value of secondary coagulation dysfunction in SAP patients was 0.937.Decision curve analysis results showed that the Logistic regression model could achieve the maximum clinical benefit when the threshold probability was in the range of 0.06 to 0.97.Conclusion A comprehensive assessment of influencing factors can comprehensively evaluate the condition of patients and identify patients at high risk of coagulation disorders at an early stage.

Objective:To investigate the impact and potential mechanisms of Sorbin and SH3 domain-containing protein 2 (Sorbs2) on ventricular arrhythmias in mice.Methods:In the animal experiments, mating was performed using six 8-week-old Sorbs2 +/- mice (3 males and 3 females) weighing 20-22 g. Wild-type (Sorbs2 +/+, n=8) and homozygous (Sorbs2 -/-, n=6) offspring were selected as experimental subjects through genotyping. Echocardiography was performed at 16 weeks of age to record cardiac function parameters in both groups. Resting-state and caffeine-dobutamine-induced electrocardiograms were also conducted. Real-time quantitative reverse transcription polymerase chain reaction was used to detect Sorbs2 messenger RNA expression in the heart, liver, spleen, lung, kidney, brain, small intestine, and skeletal muscle tissues of wild-type mice. Western blotting was employed to measure the protein expression levels of Sorbs2 and voltage-dependent sodium channel alpha subunit 1.5 (Na v1.5) in myocardial tissues from both groups. In the cell experiments, H9C2 cells were transfected with Sorbs2 small interfering RNA as the si-Sorbs2 group, with a corresponding si-negative control group established. Western blot was performed to detect the protein expression levels of Sorbs2 and Na v1.5 in both groups. Results:Sorbs2 was abundantly expressed in cardiac tissue. Compared with wild-type mice, homozygous mice exhibited larger left ventricular end-systolic diameter, along with lower left ventricular ejection fraction and fractional shortening ( P all<0.05). Resting-state electrocardiograms revealed no spontaneous arrhythmias in either group; however, homozygous mice showed shorter RR intervals but longer QRS and QTc intervals versus wild-type mice ( P all<0.05). Following caffeine and dobutamine induction, homozygous mice demonstrated a higher incidence of ventricular arrhythmias, longer arrhythmia duration, and higher ventricular arrhythmia scores than wild-type mice ( P all<0.05). Western blot analysis revealed that Na v1.5 protein expression was markedly lower in myocardial tissues of homozygous mice compared to wild-type mice. Similarly, si-Sorbs2-transfected H9C2 cells exhibited lower Na v1.5 protein levels compared to the si-negative control group ( P<0.05). Conclusion:Sorbs2 plays a critical role in maintaining normal cardiac electrophysiological function. Deficiency of Sorbs2 may lead to impaired cardiac function and increased susceptibility to ventricular arrhythmias in mice, which could be associated with reduced expression of Na v1.5 protein.

Objective:To explore the effects of estrogen receptor α (ERα) encoded by protein encoding gene ESR1 on the radiation resistance of breast cancer cells and their molecular mechanisms.Methods:The ESR1 overexpression plasmid was transfected into estrogen receptor (ER)-negative breast cancer cells. Then, the shRNA-ESR1 vector was introduced into ER-positive cell to establish models with different phenotype. The ATG5 mRNA level and protein expression levels of LC3B-I, LC3B-II, P62, FIP200, ATG5, ATG7, ATG12, Beclin1, ULK1 were detected using qPCR and Western blot techniques. Cell death was measured using flow cytometry. The radiation sensitivity was determined through the colony formation assay. The mortality of breast cancer cells under the autophagy gene knockdown and overexpression or treated with estrogen receptor inhibitor (TAM) combined with ionizing radiation were detected by trypan blue staining.Results:Under the condition of 8 Gy X-ray irradiation, the knockdown of ESR1 in ER-positive ZR75 breast cancer cells promoted cell death ( t = 3.49, 3.13, P < 0.05), while the overexpression of ESR1 in ER-negative MDA-MB-231 breast cancer cells inhibited cell death ( t = 4.16, 7.48, P < 0.05). Compared to the control group, the treatment with chloroquine increased the number of formed colonies of ESR1 knockdown ZR75 cells ( t = 8.49, P < 0.05), and inhibiting autophagy could reduce the death of ZR75 cells caused by ESR1 silencing. Under the treatment with ionizing radiation, the overexpression of ESR1 in MDA-MB-231 cells promoted protective autophagy, which, however, was reduced after ESR1 knockdown in ZR75 cells. Furthermore, it was observed that the knockdown of ATG5 in ZR75 cells was associated with reduced autophagy and an increase in cell death ( t = 4.19, 6.39, P < 0.05). In contrast, the overexpression of ATG5 in ZR75 cells reversed the increase in cell death caused by ESR1 knockdown ( t = 1.70, 4.65, P < 0.05). After the treatment of ER-positive ZR75 breast cancer cells with TAM, the expressions of ATG5 and ATG12 decreased, suggesting inhibited autophagy and an increase in cell death ( t = 18.70, P < 0.05). Furthermore, these processes were promoted by ionizing radiation ( t = 16.82, P < 0.05). Conclusions:The estrogen receptor encoded by ESR1 promotes protective autophagy of ER-positive breast cancer cells by increasing ATG5, further leading to radiation resistance in ER-positive breast cancer cells. Treatment with tamoxifen combined with ionizing radiation can increase the radiation sensitivity of ER-positive breast cancer cells.

Objective To investigate the clinical, biochemical, pathological, disease course, and prognostic features of drug-induced liver injury (DILI) patients with different types of bile duct injury. Methods Four patients who were diagnosed with bile duct injury-type DILI by liver biopsy in Shijiazhuang Fifth Hospital, from March 2015 to October 2010 were selected, and related data were collected, including clinical data, laboratory examinations, radiological examination, and prognosis.The semi-quantitative score was determined for liver pathological morphology, and each indicator was compared between the four patients. Results Bile duct injury-type DILI was more common in female patients, and most patients tended to have a good prognosis.Clinical symptoms, liver biochemical parameters, and prognosis varied with the site, grade, scope, regeneration, and repair of bile duct injury. Conclusion Liver biopsy is still the gold standard for making a definite diagnosis of bile duct injury-type DILI, understanding the condition of lesions, and judging the prognosis of this disease.

Objective To explore the influence of WeChat platform rehabilitation guidance mode on refracture of osteoporotic fracture patients.Methods Totally 100 osteoporotic fracture patients admitted to the Department of Orthopedics of the hospital from 2018 to 2019 were selected and randomly divided into control group and experimental group with 50 patients in each group.The control group adopted the conventional discharge rehabilitation guidance mode,and the experimental group implemented WeChat platform rehabilitation guidance mode on this basis,including WeChat platform construction and detailed intervention mode.The changes of bone mineral density and the recurrence rate of osteoporotic fracture were compared between the two groups at admission and after 3 years of follow-up.Results There were 7 cases of lost follow-up in the experimental group,and there were 6 cases of lost follow-up in the control group.After 3 years,the bone mineral density of the experimental group was significantly higher than that of the control group,and the recurrence fracture rate was significantly lower than that of the control group(P<0.05).Conclusion The application of WeChat platform rehabilitation guidance mode can effectively improve bone density and reduce the incidence of refracture in osteoporotic fracture patients.

Objective:To explore the related factors influencing prognosis of patients with grade Ⅲ cholangitis with myocardial injury.Methods:91 patients with grade III cholangitis complicated with myocardial injury treated in the emergency department of Beijing Friendship Hospital Affiliated to Capital Medical University from June 2015 to December 2020 were collected retrospectively. They were divided into endoscopic retrograde cholangiopancreatography (ERCP) group ( n=75) and non-ERCP group ( n=16) according to whether ERCP was performed. According to 28-day survival patients were divided into survival group ( n=56) and death group ( n=35). The level of serum cardiac troponin T (cTnT), cardiac troponin I (cTnI), creatine kinase isoenzyme (CK-MB), N terminal pro-brain natriuretic peptide (NT-proBNP), white blood cell (WBC), platelet (PLT), serum creatinine (Scr), alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), International Standardized Ratio (INR), Glasgow Coma Score (GCS) at different time points were detected and the risk factors influencing the prognosis of patients were analyzed. Results:The cTnT ( P=0.018), NT-proBNP ( P<0.001), PLT ( P=0.016), GCS score ( P=0.07) on day 3 and cTnI ( P=0.027), cTnT ( P=0.002), CK-MB ( P=0.046), NT-proBNP ( P<0.001), PLT ( P=0.041), GCS score ( P<0.001) on day 7 in the ERCP group were significantly different with the non-ERCP group respectively. The survival rate within 28 days of the ERCP group was significantly different from that in the non-ERCP group ( P<0.001). The cTnT ( P=0.006) on day 1, the cTnT ( P=0.021), NT-proBNP ( P=0.02), WBC ( P=0.037), GCS score ( P<0.001) on day 3, and the cTnI ( P=0.029), cTnT ( P=0.008), CK-MB ( P<0.001), PLT ( P=0.008), NT-proBNP ( P=0.004), GCS ( P<0.001) on day 7 in survival group were significantly different from the death group. Logistic regression showed that the mean value of myocardial injury markers and ERCP process were significantly correlated with the 28 days survival rate. Conclusions:In patients with Grade Ⅲ cholangitis-related myocardial injury, the levels of myocardial injury markers, NT-proBNP, platelet (PLT) and Glasgow Coma Score (GCS) are related to mortality. ERCP for patients can significantly improve 28 days survival and prognosis.